[Federal Register: June 8, 2004 (Volume 69, Number 110)]
[Notices]
[Page 32010-32011]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr08jn04-75]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. 2002D-0237]
International Conference on Harmonisation; Evaluation of
Stability Data; Availability
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice.
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SUMMARY: The Food and Drug Administration (FDA) is announcing the
availability of a guidance entitled ``Q1E Evaluation of Stability
Data.'' The guidance was prepared under the auspices of the
International Conference on Harmonisation of Technical Requirements for
Registration of Pharmaceuticals for Human Use (ICH). This guidance is a
supplement to an ICH guidance entitled ``Q1A(R2) Stability Testing of
New Drug Substances and Products,'' which was revised from Q1A(R) and
published in the Federal Register of November 21, 2003 (68 FR 65717).
It is intended to provide guidance on how to use stability data,
generated in accordance with the principles outlined in Q1A(R2), to
propose a retest period for the drug substance and a shelf life for the
drug product.
DATES: The guidance is effective June 8, 2004. Submit written or
electronic comments at any time.
ADDRESSES: Submit written comments on the guidance to the Division of
Dockets Management (HFA-305), Food and Drug Administration, 5630
Fishers Lane, rm. 1061, Rockville, MD 20852. Submit electronic comments
to http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/dockets/ecomments. Submit written requests for
single copies of the guidance to the Division of Drug Information (HFD-
240), Center for Drug Evaluation and Research, Food and Drug
Administration, 5600 Fishers Lane, Rockville, MD 20857, or the Office
of Communication, Training, and Manufacturers Assistance (HFM-40),
Center for Biologics Evaluation and Research, Food and Drug
Administration, 1401 Rockville Pike, Rockville, MD 20852-1448, 301-827-
3844. Send two self-addressed adhesive labels to assist the office in
processing your requests. Requests and comments should be identified
with the docket number found in brackets in the heading of this
document. See the SUPPLEMENTARY INFORMATION section for electronic
access to the guidance.
FOR FURTHER INFORMATION CONTACT:
Regarding the guidance: Chi-wan Chen, Center for Drug Evaluation
and Research (HFD-830), Food and Drug Administration, 5600 Fishers
Lane, Rockville, MD 20857, 301-827-2001; or Andrew Shrake, Center for
Biologics Evaluation and Research (HFM-345), Food and Drug
Administration, 1401 Rockville Pike, Rockville, MD 20852-1148, 301-402-
4635.
Regarding the ICH: Janet Showalter, Office of International
Programs (HFG-1), Food and Drug Administration, 5600 Fishers Lane,
Rockville, MD 20857, 301-827-0864.
SUPPLEMENTARY INFORMATION:
I. Background
In recent years, many important initiatives have been undertaken by
regulatory authorities and industry associations to promote
international harmonization of regulatory requirements. FDA has
participated in many meetings designed to enhance harmonization and is
committed to seeking scientifically based harmonized technical
procedures for pharmaceutical development. One of the goals of
harmonization is to identify and then reduce differences in technical
requirements for drug development among regulatory agencies.
ICH was organized to provide an opportunity for tripartite
harmonization initiatives to be developed with input from both
regulatory and industry representatives. FDA also seeks input from
consumer representatives and others. ICH is concerned with
harmonization of technical requirements for the registration of
[[Page 32011]]
pharmaceutical products among three regions: The European Union, Japan,
and the United States. The six ICH sponsors are the European
Commission, the European Federation of Pharmaceutical Industries
Associations, the Japanese Ministry of Health, Labour, and Welfare, the
Japanese Pharmaceutical Manufacturers Association, the Centers for Drug
Evaluation and Research and Biologics Evaluation and Research, FDA, and
the Pharmaceutical Research and Manufacturers of America. The ICH
Secretariat, which coordinates the preparation of documentation, is
provided by the International Federation of Pharmaceutical
Manufacturers Associations (IFPMA).
The ICH Steering Committee includes representatives from each of
the ICH sponsors and the IFPMA, as well as observers from the World
Health Organization, Health Canada's Health Products and Food Branch,
and the European Free Trade Area.
In the Federal Register of June 14, 2002 (67 FR 40949), FDA
published a draft tripartite guidance entitled ``Evaluation of
Stability Data.'' The notice gave interested persons an opportunity to
submit comments by August 1, 2002.
After consideration of the comments received and revisions to the
guidance, a final draft of the guidance was submitted to the ICH
Steering Committee and endorsed by the three participating regulatory
agencies in February 2003.
This guidance complements an ICH guidance entitled ``Q1A(R2)
Stability Testing of New Drug Substances and Products,'' which was
revised from Q1A(R) and published in the Federal Register of November
21, 2003. The guidance is intended to provide recommendations on how to
use stability data, generated in accordance with the principles
outlined in Q1A(R2), to propose a retest period for the drug substance
and a shelf life for the drug product.
The recommendations on the evaluation and statistical analysis of
stability data provided in Q1A(R2) are brief in nature and limited in
scope. Although Q1A(R2) states that regression analysis is an
acceptable approach to analyzing quantitative stability data for retest
period or shelf life estimation and recommends that a statistical test
for batch poolability be performed using a level of significance of
0.25, it includes few details. In addition, Q1A(R2) does not cover
situations where multiple factors are involved in a full- or reduced-
design study. This guidance provides a clear explanation of the
expectations when proposing a retest period or shelf life and storage
conditions based on the evaluation of stability data for both
quantitative and qualitative test attributes. It outlines
recommendations for establishing a retest period or shelf life based on
stability data from single or multifactor and full- or reduced-design
studies. The guidance further describes when and how limited
extrapolation can be undertaken to propose a retest period or shelf
life beyond the observed range of data from the long-term storage
condition.
This guidance represents the agency's current thinking on this
topic. It does not create or confer any rights for or on any person and
does not operate to bind FDA or the public. An alternative approach may
be used if such approach satisfies the requirements of the applicable
statutes and regulations.
II. Comments
Interested persons may submit to the Division of Dockets Management
(see ADDRESSES) written or electronic comments on the guidance. Submit
a single copy of electronic comments or two paper copies of any mailed
comments, except that individuals may submit one paper copy. Comments
are to be identified with the docket number found in brackets in the
heading of this document. The guidance and received comments may be
seen in the Division of Dockets Management between 9 a.m. and 4 p.m.,
Monday through Friday.
III. Electronic Access
Persons with access to the Internet may obtain the document at
http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/ohrms/dockets/default.htm, http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/cder/guidance/index.htm, or http://www.fda.gov/cber/publications.htm.
Dated: May 29, 2004.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 04-12889 Filed 6-7-04; 8:45 am]
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